Interferon-alpha 2b combined with daily ketoprofen administration improves virological response in chronic hepatitis C: a prospective and randomised trial

Abstract

Background-Less than 15% of patients with chronic hepatitis C show a sustained virological response to interferon treatment. Aim-To evaluate the eYcacy and safety of diVerent doses of ketoprofen combined with interferon-2b in the treatment of chronic hepatitis C. Patients/Methods-Seventy compensated patients with chronic hepatitis C received interferon-2b 3 million units three times a week for six months. They were randomly assigned to: group 1 (n = 23), interferon2b alone; group 2 (n = 23), interferon-2b plus 200 mg ketoprofen three times a week; group 3 (n = 24), interferon-2b plus 200 mg ketoprofen twice a day. Complete and sustained responses were defined as normal serum alanine aminotransferase levels and negative serum hepatitis C virus RNA at six and 12 months respectively. Results-Complete and sustained responses were similar in groups 1 and 2: 10% v 5% and 5% v 0% respectively. In group 3, complete response was 29% (p = 0.13 v group 1 and p = 0.04 v group 2) and sustained response was 26% (p = 0.07 v group 1 and p = 0.01 v group 2). Overall, adverse events were similar in the three groups. However, 'flu-like syndrome was less common in group 2 (30%) and group 3 (37%) than in group 1 (77%) (p = 0.01). Conclusions-Twice daily ketoprofen administration combined with interferon2b produced an increase in complete and sustained responses. Although the combination of interferon-2b with ketoprofen was well tolerated and decreased the incidence of 'flu-like syndrome, it is advisable to monitor possible non-steroid antiinflammatory drug hepatotoxicity.

Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways

“…[34][35][36][37] Some reports have indicated the failure of NSAIDs and interferon combination therapy in improving interferon-resistant chronic hepatitis C, 34,38 whereas other authors, using ketoprofen plus interferon, have reported an improved virological response in chronic hepatitis C patients. 35 Giambartolomei et al 39,40 reported that indomethacin potentiates the interferon-␣ signaling pathway by increasing signal transducer and activator of transcription 1 phosphorylation in vitro, improving cellular response. It must be noted that the aforementioned studies used NSAIDs with different biochemical activities and did not include comparable groups of HCV patients.…”

Side Effects of Interferon-α Therapy

“…If necessary, symptoms can generally be managed either by administration of agents such as acetaminophen and cyclo-oxygenase inhibitors prior to IFN-a or by dosereduction. There are no indications that administration of these agents adversely interfere with the antitumor activity of IFN-a 7,8 .…”

Meloxicam as an adjuvant to peginterferon‐α‐2a and ribavirin treatment for genotype 1 chronic hepatitis C: A randomized trial

“…The ketoprofen group showed a significantly higher SVR rate (32.5%) than the control group (10%). Munoz et al . also showed that 6‐month interferon‐α‐2b therapy combined with ketoprofen was superior to interferon alone, for the treatment of naïve patients (SVR: 26% vs 5%).…”

“…Non‐steroidal anti‐inflammatory drugs (NSAIDs) are another class of drugs that may act as adjuvants for the treatment of chronic hepatitis C. In vitro studies have indicated that NSAIDs not only potentiate interferon signaling, via signal transducer and activator of transcription (STAT)1 phosphorylation, but also inhibited HCV RNA replication in Huh7 replicon cells . Two randomized trials showed that interferon monotherapy, combined with ketoprofen, increased the SVR rate, compared with interferon alone …”

“…9 Two randomized trials showed that interferon monotherapy, combined with ketoprofen, increased the SVR rate, compared with interferon alone. 10,11 Meloxicam is an NSAID that preferentially inhibits cyclooxygenase (COX)-2 and has a high therapeutic index. 12 In a pilot study, 13 we administered meloxicam for 8 weeks, in conjunction with peginterferon, to patients with chronic hepatitis C and evaluated the effect of this drug on the change in blood cell counts.…”